In our Cellular Conversations blog post series, we described the role of biochemical, mechanical, and electrical signals in bone tissue repair. This post explores the clinical applications of electrical stimulation in bone repair, including mechanisms and future prospects.
PART 4: Understanding Electrical Stimulation in Bone Repair
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Figure 1. Electrical stimulation methods for bone growth and repair. Invasive stimulators: (A) Direct current electrical stimulation (DCES), Non-invasive stimulators: (B) Inductive coupling, and (C) capacitive coupling. Source: (Khalifeh et al., 2018) |
As discussed in greater detail in the 3rd post in this series here, these techniques leverage, enhance, or mimic the body’s natural electrical fields to accelerate bone healing. Electrical stimulation increases release of growth factors such as IGF-2 (Insulin-Like Growth Factor 2), bone morphogenetic proteins (BMPs), and TGF-β1 (Transforming Growth Factor beta 1), which promote cell proliferation, and callus formation and maturation. Direct current stimulation also supports osteoblast proliferation by reducing oxygen levels and increasing pH, creating a slightly alkaline environment that further encourages callus formation and facilitates bone repair.
Based on clinical application, these techniques can be classified as: 1) invasive, 2) semi-invasive, or 3) non-invasive.
Invasive Electrical Stimulation (Figure 1A)
Surgically implantable devices deliver continuous direct current stimulation to the site of repair.
Devices are implanted in subcutaneous or intramuscular space with electrodes placed at the site of bone repair.
Used in challenging cases where traditional healing methods have failed.
Surgical implantation carries risks of infection, inflammation, or tissue discomfort.
Additional procedures are required to remove the device once treatment is complete.
FDA-approved devices are on the market.
Semi-invasive Stimulation
Percutaneous electrodes are inserted through the skin to the fracture site and remain connected to an external power source.
Doctors can apply and remove the device without the requirement for an open, invasive, surgical procedure.
Increased risk of infection, inflammation, or discomfort at the region of lead insertion.
Not currently FDA-approved.
Non-invasive Stimulation
External devices, in the form of wearable patches or braces, deliver electrical currents to the affected area, promoting bone healing without the need for surgery.
The mechanism of action is thought to be the increase in cytosolic calcium levels created by electrical activation of voltage-gated calcium channels.
Inductive coupling (Figure 1B) involves a current generator and electromagnetic coils which are held in place by a brace or belt.
Pulsed Electromagnetic Field devices generate a pulsed magnetic field near the treatment site, typically worn for 3 – 8 hrs/day for 3 – 9 months.
Controlled Magnetic Field devices generate both pulsed and static magnetic fields near the treatment site and are typically worn for 30 minutes a day for 9 months.
Capacitive coupling (Figure 1C) devices generate an electrical field between two conductive plates or pads that are positioned on the skin covering opposite sides of the target site.
Ongoing research efforts to understand the roles of all methods of cell signaling (biochemical, mechanical, and electrical) will lead to more precise and effective treatments for fracture and bony fusions. At Molecular Matrix, Inc., we utilize our knowledge of cell signaling to develop innovative methods for bone regeneration. To learn more about Molecular Matrix, Inc.; click here.
References:
Ali, S., Belmont, P., & Muir, J. (2020). Proposed Reclassification of Non-Invasive Bone Growth Stimulators (BGSs). FDA, Orthopaedic and Rehabilitation Devices Panel Meeting, 1–38.
deVet, T., Jhirad, A., Pravato, L., & Wohl, G. R. (2021). Bone Bioelectricity and Bone-Cell Response to Electrical Stimulation: A Review. Critical Reviews in Biomedical Engineering, 49(1), 1–19. https://doi.org/10.1615/CritRevBiomedEng.2021035327
Dolkart, O., Kazum, E., Rosenthal, Y., Sher, O., Morag, G., Yakobson, E., Chechik, O., & Maman, E. (2021). Effects of focused continuous pulsed electromagnetic field therapy on early tendon-to-bone healing: Rat supraspinatus detachment and repair model. Bone & Joint Research, 10(5), 298–306. https://doi.org/10.1302/2046-3758.105.BJR- 2020-0253.R2
Goldstein, C., Sprague, S., & Petrisor, B. A. (2010). Electrical Stimulation for Fracture Healing: Current Evidence. Journal of Orthopaedic Trauma, 24(Supplement 1), S62– S65. https://doi.org/10.1097/BOT.0b013e3181cdde1b
Griffin, M., & Bayat, A. (2011). Electrical Stimulation in Bone Healing: Critical Analysis by Evaluating Levels of Evidence. Eplasty, 11, 303–353.
Khalifeh, J. M., Zohny, Z., MacEwan, M., Stephen, M., Johnston, W., Gamble, P., Zeng, Y., Yan, Y., & Ray, W. Z. (2018). Electrical Stimulation and Bone Healing: A Review of Current Technology and Clinical Applications. IEEE Reviews in Biomedical Engineering, 11, 217–232. https://doi.org/10.1109/RBME.2018.2799189
Leppik, L., Oliveira, K. M. C., Bhavsar, M. B., & Barker, J. H. (2020). Electrical stimulation in bone tissue engineering treatments. European Journal of Trauma and Emergency Surgery, 46(2), 231–244. https://doi.org/10.1007/s00068-020-01324-1
Nicksic, P. J., Donnelly, D. T., Hesse, M., Bedi, S., Verma, N., Seitz, A. J., Shoffstall, A. J., Ludwig, K. A., Dingle, A. M., & Poore, S. O. (2022). Electronic Bone Growth Stimulators for Augmentation of Osteogenesis in In Vitro and In Vivo Models: A Narrative Review of Electrical Stimulation Mechanisms and Device Specifications. Frontiers in Bioengineering and Biotechnology, 10, 793945. https://doi.org/10.3389/fbioe.2022.793945
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